Professor (Teaching) of Pediatrics (Neonatology) and, by courtesy, of Obstetrics and Gynecology

Pediatrics - Neonatal and Developmental Medicine

Bio

Bio

Gary L. Darmstadt, MD, MS, is Associate Dean for Maternal and Child Health, and Professor of Neonatal and Developmental Pediatrics in the Department of Pediatrics at the Stanford University School of Medicine. Previously Dr. Darmstadt was Senior Fellow in the Global Development Program at the Bill & Melinda Gates Foundation (BMGF), where he led a cross-foundation initiative on Women, Girls and Gender, assessing how addressing gender inequalities and empowering women and girls leads to improved gender equality as well as improved health and development outcomes. Prior to this role, he served as BMGF Director of Family Health, leading strategy development and implementation across nutrition, family planning and maternal, newborn and child health.

Darmstadt was formerly Associate Professor and Founding Director of the International Center for Advancing Neonatal Health in the Department of International Health at the Johns Hopkins Bloomberg School of Public Health. He has trained in Pediatrics at Johns Hopkins University, in Dermatology at Stanford University, and in Pediatric Infectious Disease as a fellow at the University of Washington, Seattle, where he was Assistant Professor in the Departments of Pediatrics and Medicine. Dr. Darmstadt left the University of Washington to serve as Senior Research Advisor for the Saving Newborn Lives program of Save the Children-US, where he led the development and implementation of the global research strategy for newborn health and survival, before joining Johns Hopkins.

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Projects

Lancet Series on the Next Generation of Gender Equality, Stanford University (11/1/2015 - Present)

Major new visibility on the importance of investing in women and girls has created new opportunities to accelerate advances in health and development of nations around the world. A more intentional approach to addressing gender norms and gender inequalities in policies, programs and research is critical to this effort. We are working with the Lancet to develop a series of papers on the following topics:

1. Unlocking human potential through shaping gender norms2. Unlocking gender norm data3. Unlocking gender norm change to achieve health and development impact at scale4. Unlocking gender norm change in systems to ensure sustainability of health and development impact5. Unlocking global action to shape gender norms and optimize health and development across the life course

Through these papers, we hope to i) propose a conceptual framework for associations between gender norms, gender inequalities and health and development, ii) place the development and shaping of gender norms and gender equality in historical perspective, iii) define the global scope and size of issues of unhealthy gender norms and gender inequalities across the life course (with a focus on early childhood, adolescence, and early and late adulthood), including costs of inaction, in high, middle and low-income countries, iv) synthesize the existing evidence for approaches to shape gender norms, v) quantify the benefits of addressing unhealthy gender norms and gender inequalities for women, girls, men and boys, vi) calculate the cost to implement these solutions at scale, vii) define global metrics, and viii) develop a concrete action plan to advance healthy gender norms as well as health and development of women, men, girls and boys, and of societies worldwide.

WaSH Up! is a partnership between Sesame Street, World Vision, and Stanford University to reduce child disease and death by ensuring children have access to safe water and sanitation by practice healthy behaviors relators to water, sanitation and hygiene (WaSH). Sesame Workshop has worked to created a new Muppet character named Raya, a girl ambassador who promotes safe WaSH practices. Sesame Workshop with World Vision announces a commitment to roll out WaSH Up! across 15 countries in the next six years. The team at Stanford University will be the primary evaluator and research partner, investigating school- and community-based interventions. Stanford will contribute a strong theoretical grounding leading to improvementsin program design and impact, to design a rigorous evaluation of the program?s impacts, and toidentify and pursue complementary research opportunities.

Location

Lusaka, Zambia

Collaborators

Jenna Davis, Associate Professor of Civil and Environmental Engineering and Senior Fellow at the Woods Institute for the Environment, Stanford University

Creating a Scalable Model to End Poverty: Delivery of an Integrated Childhood Development Strategy in Rural China

To building on existing programs and collaborations between the Rural Education and Action Program (REAP) and the Chinese government to pilot, deliver, and evaluate an integrated, community-based program for children 0-3 years in existing parenting center in rural China.

Location

Shaanxi, China

Collaborators

Scott Rozelle, Helen C. Farnsworth Professor in International Agricultural Policy and Senior Fellow at the Stanford Institute for Economic Policy Research, Stanford University

The Lancet Series: Advancing Early Childhood Development: from Science to Scale, The Lancet

The 2016 Lancet Early Childhood Development Series highlights early childhood development at a time when it has been universally endorsed in the 2030 Sustainable Development Goals. This Series considers new scientific evidence for interventions, building on the findings and recommendations of previous Lancet Series on child development (2007, 2011), and proposes pathways for implementation of early childhood development at scale. The Series emphasises 'nurturing care', especially of children below three years of age, and multi-sectoral interventions starting with health, which can have wide reach to families and young children through health and nutrition.

Location

Global

Learning from Ananya - Scaling Up Improved Family Health, Stanford University (12/2016)

The Stanford University (SU) School of Medicine ?Co-Creation? group will employ a mixed quantitative and qualitative methods approach to analyze/mine existing data sets, dialogue with implementers and evaluators, and share the knowledge and data gained from the Bill and Melinda Gates Foundation (BMGF)-funded Ananya program in Bihar, India. SU will conduct this analysis to disseminate learning from Ananya to inform the scale-up of national and global family health (reproductive, maternal, newborn and child health and nutrition, RMNCHN) interventions. In close collaboration with the BMGF India Country Office (ICO), and Ananya implementation and evaluation partners, SU will analyze and synthesize a range of existing data sources, which ? together with the primary qualitative data we will collect ? will inform the development of core peer-reviewed articles and additional papers and policy briefs. These insights will help the BMGF Program Strategy Teams (PSTs), the government of Bihar, Ananya grantees, and the broader global health community make evidence-informed decisions to optimize the coverage, quality and impact of their investments in improving maternal and child health outcomes.

Location

Collaborators

Wolfgang Munar, Research Professor, Department of Global Health, George Washington University

A Mobile Autism Risk Initiative (AMARI) to detect Autism Spectrum Disorder in all Bangladeshi children under the age of 4., Dhaka Shishu Hospital, Stanford University

There is a rising epidemic of autism around the world that now affects an estimated 1 in 68 children in the United States, with similar prevalence rates found in many countries worldwide. Multiple barriers exist to identification and treatment of at-risk children. Our goal is to identify and diagnose every child with autism in Bangladesh before the age of 4 using mobile machine-learning technology that analyzes home videos and a short caregiver-directed questionnaire in minutes. This technology has the potential to leapfrog over existing cultural, language, technology, and health workforce barriers to ensure accurate identification of children with autism early in life. If validated, this proof-of-concept initiative to screen and diagnose children with autism could be extended to other under-resourced countries and to other neuro-developmental conditions thereby expanding the reach and impact of services that are central to achievement of the Sustainable Development Goals outlined in the recently launched Lancet Series on Advancing Early Childhood Development.

Abstract

Preterm birth (PTB), or the delivery prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. Although twin studies estimate that maternal genetic contributions account for approximately 30% of the incidence of PTB, and other studies reported fetal gene polymorphism association, to date no consistent associations have been identified. In this study, we performed the largest reported genome-wide association study analysis on 1,349 cases of PTB and 12,595 ancestry-matched controls from the focusing on genomic fetal signals. We tested over 2 million single nucleotide polymorphisms (SNPs) for associations with PTB across five subpopulations: African (AFR), the Americas (AMR), European, South Asian, and East Asian. We identified only two intergenic loci associated with PTB at a genome-wide level of significance: rs17591250 (P?=?4.55E-09) on chromosome 1 in the AFR population and rs1979081 (P?=?3.72E-08) on chromosome 8 in the AMR group. We have queried several existing replication cohorts and found no support of these associations. We conclude that the fetal genetic contribution to PTB is unlikely due to single common genetic variant, but could be explained by interactions of multiple common variants, or of rare variants affected by environmental influences, all not detectable using a GWAS alone.

Abstract

Achieving gender equality in education is an important development goal. We tested the hypothesis that the gender gap in adolescent education is accentuated by illnesses among young children in the household.Using Demographic and Health Surveys on 41?821 households in 38 low- and middle-income countries, we used linear regression to estimate the difference in the probability adolescent girls and boys were in school, and how this gap responded to illness episodes among children <5 years old. To test the hypothesis that investments in child health are related to the gender gap in education, we assessed the relationship between the gender gap and national immunization coverage.In our sample of 120?708 adolescent boys and girls residing in 38 countries, girls were 5.08% less likely to attend school than boys in the absence of a recent illness among young children within the same household (95% confidence interval [CI], 5.50%-4.65%). This gap increased to 7.77% (95% CI, 8.24%-7.30%) and 8.53% (95% CI, 9.32%-7.74%) if the household reported 1 and 2 or more illness episodes, respectively. The gender gap in schooling in response to illness was larger in households with a working mother. Increases in child vaccination rates were associated with a closing of the gender gap in schooling (correlation coefficient = 0.34, P = .02).Illnesses among children strongly predict a widening of the gender gap in education. Investments in early childhood health may have important effects on schooling attainment for adolescent girls.

Abstract

Group B Streptococcus (GBS) infection is a leading cause of death in newborns in developed countries. Data on burden of GBS in Asian countries is lacking. This study aimed to understand i) rate of maternal recto-vaginal GBS carriage, ii) vertical transmission of GBS as determined by culturing ear, umbilicus and nasal swabs, and iii) distribution of GBS serotypes. This prospective observational study was conducted from September 2012 to November 2013 at Kumudini Hospital, a secondary level hospital, at Mirzapur, Bangladesh. The study enrolled pregnant women who visited the out-patient clinic for antenatal care (ANC) and/or delivered a child at the in-patient department of Kumudini Hospital, and babies born to these mothers. Among 1151 enrolled pregnant women, 172 (15%; 95% CI: 13%-17%) carried GBS and 26 (38%; 95% CI: 27%-51%) babies born to the mothers (n=68) with carriage had GBS on their body surface, indicating vertical transmission. Typing of the isolates (n=172) identified all 10 GBS serotypes, most commonly Ia (40%; 69/172), V (23%; 40/172), II (14%; 24/172), and III (12%; 20/172). This study shows that Bangladesh has all the ingredients for invasive GBS diseases, including colonization of mothers by invasive serotypes and vertical transmission to babies.

Abstract

In recent years, an increasing prevalence of macrolide resistance among pneumococci in Bangladesh has been observed. However, the scenario remains incomplete, as few isolates (<1%) are available from pneumonia cases and most pneumococcal meningitis cases (>80%) are culture-negative. This study optimised a triplex PCR method to detect macrolide resistance genes (MRGs) (mefA and ermB) and cpsA from culture-negative pneumococcal cases to predict the prevalence and level of macrolide resistance.The presence of MRGs among pneumococcal strains (n=153) with a wide range of erythromycin MICs (<0.5 to ?256mg/L) was determined by PCR. Triplex PCR was validated by simultaneous detection of MRG(s) and cpsA in culture-negative clinical specimens and corresponding isolates. The known impact of the presence of specific MRG(s) on MICs of strains was used to predict the MICs of non-culturable strains based on the presence/absence of MRG(s) in the specimens.None of the erythromycin-susceptible isolates possessed any of the MRGs, and all non-susceptible strains had ?1 MRG. MICs were 2-16mg/L and ?256mg/L for 93% of strains with mefA and ermB, respectively, whereas 100% of isolates with both genes had MICs?256mg/L. PCR for body fluids showed 100% concordance with corresponding isolates when tested for MRG(s) in parallel.Erythromycin MICs can be predicted for non-culturable strains with 93-100% precision based on detection of ermB and/or mefA. This method will be useful for establishing comprehensive surveillance for macrolide resistance among pneumococci, specifically in the population with prior antibiotic use.

Abstract

The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling-based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2-dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.

Abstract

This article presents evidence supporting the hypothesis that promoting gender equality and women's and girls' empowerment (GEWE) leads to better health and development outcomes. We reviewed the literature across six sectors-family planning (FP); maternal, newborn and child health (MNCH); nutrition; agriculture; water, sanitation and hygiene; and financial services for the poor-and found 76 studies from low and middle-income countries that met our inclusion criteria. Across these studies, we identified common GEWE variables that emerged repeatedly as significant predictors of sector outcomes. We grouped these variables into 10 thematic categories, which we termed 'gender-related levers'. These levers were then classified by the strength of evidence into Wedges, Foundations and Facilitators. Wedges are gender-related levers that had strong associations with improved outcomes across multiple sectors. They include: 'control over income/assets/resources', 'decision-making power' and 'education'. Elements of these levers overlap, but combined, they encapsulate agency. Increasing female agency promotes equality and broadly improves health and development for women, their families and their communities. The second classification, Foundations, displayed strong, positive associations across FP, MNCH and nutrition. Foundations have a more proximal relationship with sector outcomes and include: 'equitable interpersonal relationships', 'mobility' and 'personal safety'. Finally, the third group of levers, Facilitators, was associated with improved outcomes in two to three sectors and include: 'access to information', 'community groups', 'paid labour' and 'rights'. These levers make it easier for women and girls to achieve their goals and are more traditional elements of development programmes. Overall, gender-related levers were associated with improvements in a variety of health and development outcomes. Furthermore, these associations were cross-sectoral, suggesting that to fully realize the benefits of promoting GEWE, the development community must collaborate in co-ordinated and integrated ways across multiple sectors. More research is needed to identify the mechanisms by which gendered interventions work and under what circumstances.

Abstract

Group B Streptococcus (GBS) is a predominant cause of early-onset neonatal sepsis globally; however, the impact of this organism on the health of newborns in South Asia is debated, due in part to a paucity of community-based assessments. We estimated the prevalence and serotypes of GBS colonization of the umbilical cord stump and the association of colonization with mortality in a population-based cohort of newborns in rural Sylhet District, Bangladesh.Umbilical cord swabs were collected from 646 newborns up to 3 times within the first week after birth (ages <24 hours, ~3 days, ~6 days) and processed to identify GBS serotypes.GBS was isolated from 6.3% (41/646) of newborns. Sixty-one percent of the GBS colonization occurred in neonates within 24 hours of delivery. Serotypes VII (37.1%, n = 13/36) and Ia (33.3%, n = 12/36) were the most predominant colonizing GBS isolates. Other detected serotypes were Ib (11.1%, n = 4/36), II (11.1%, n = 4/36), V (5.6%, n = 2/36) and VI (2.8%, n = 1/36). Mortality risk among newborns with GBS colonization was 6.6 (95% confidence interval: 2.1-20.4) times higher than for those without GBS.The overall prevalence of GBS colonization was lower than in settings, where GBS is a predominant etiology of neonatal illness. In addition, the GBS serotype distribution differed from that reported in the developed part of the world. However, further studies are needed to understand the true burden of GBS-related illness. Mortality risk was substantially increased in the presence of GBS on the umbilical stump, providing support for chlorhexidine antisepsis to the cord to prevent colonization of invasive pathogens.

Abstract

Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4(+) and CD8(+) T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal Tbet(+)CD4(+) T cells, CD8(+) T cells, B cells, and CD56(lo)CD16(+) NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes.

Abstract

Building on long-term benefits of early intervention (Paper 2 of this Series) and increasing commitment to early childhood development (Paper 1 of this Series), scaled up support for the youngest children is essential to improving health, human capital, and wellbeing across the life course. In this third paper, new analyses show that the burden of poor development is higher than estimated, taking into account additional risk factors. National programmes are needed. Greater political prioritisation is core to scale-up, as are policies that afford families time and financial resources to provide nurturing care for young children. Effective and feasible programmes to support early child development are now available. All sectors, particularly education, and social and child protection, must play a role to meet the holistic needs of young children. However, health provides a critical starting point for scaling up, given its reach to pregnant women, families, and young children. Starting at conception, interventions to promote nurturing care can feasibly build on existing health and nutrition services at limited additional cost. Failure to scale up has severe personal and social consequences. Children at elevated risk for compromised development due to stunting and poverty are likely to forgo about a quarter of average adult income per year, and the cost of inaction to gross domestic product can be double what some countries currently spend on health. Services and interventions to support early childhood development are essential to realising the vision of the Sustainable Development Goals.

Abstract

Neonatal infections are estimated to account for a quarter of the 2·8 million annual neonatal deaths, as well as approximately 3% of all disability-adjusted life-years. Despite this burden, few data are available on incidence, aetiology, and outcomes, particularly regarding impairment. We aimed to develop guidelines for improved scientific reporting of observational neonatal infection studies, to increase comparability and to strengthen research in this area. This checklist, Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE- NI), is an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. STROBE-NI was developed following systematic reviews of published literature (1996-2015), compilation of more than 130 potential reporting recommendations, and circulation of a survey to relevant professionals worldwide, eliciting responses from 147 professionals from 37 countries. An international consensus meeting of 18 participants (with expertise in infectious diseases, neonatology, microbiology, epidemiology, and statistics) identified priority recommendations for reporting, additional to the STROBE statement. Implementation of these STROBE-NI recommendations, and linked checklist, aims to improve scientific reporting of neonatal infection studies, increasing data utility and allowing meta-analyses and pathogen-specific burden estimates to inform global policy and new interventions, including maternal vaccines.

Abstract

To validate a Rapid Neurodevelopmental Assessment (RNDA) tool for use by child health professionals to determine neurodevelopmental impairments (NDIs) in young adolescents aged 10-16?years in Bangladesh.In a convenience sample of community children (n = 47), inter-rater reliability was determined between four testers, and concurrent validity was determined by simultaneous administration of an intelligence quotient (IQ) test (Wechsler Intelligence Scale for Children, Revised) by a child psychologist.Inter-rater reliability was excellent between the testers on the 47 children administered the RNDA (kappa = 1.00). Significantly lower IQ scores were obtained in those identified with 'any (>1) NDI' (n = 34) compared with those with no NDI (n = 13) on Verbal IQ (P-value < 0.0001), Performance IQ (P-value < 0.0001) and Full-scale IQ (P-value < 0.0001) scores on the Wechsler Intelligence Scale for Children, Revised.The RNDA shows promise as a tool for use by child health professionals for identifying NDIs in young adolescents aged 10-16?years. A larger study sample is needed to determine its usefulness for identification of some impairments not found in the study population, i.e. gross motor, fine motor, hearing and seizures.

Abstract

Six multiplex-compatible PCR primers were designed to distinguish Streptococcus pneumoniae serotypes within serogroup 18 from culturable/nonculturable pneumococcal specimens, with no cross-reactivity with other serotypes and respiratory organisms. These primers will aid in the generation of better data on vaccine/nonvaccine serotypes in invasive and carriage pneumococcal surveillance and contribute to future vaccine formulation and impact studies.

Abstract

As the Sustainable Development Goals are adopted by United Nations member states, children with congenital disorders remain left behind in policies, programs, research, and funding. Although this finding was recognized by the creation and endorsement of the 63rd World Health Assembly Resolution in 2010 calling on United Nations member states to strengthen prevention of congenital disorders and the improvement of care of those affected, there has been little to no action since then. The Sustainable Development Goals call for the global health and development community to focus first and foremost on the most vulnerable and those left behind in the Millennium Development Goal era. To maximize the opportunity for every woman and couple to have a healthy child and to reduce the mortality and severe disability associated with potentially avoidable congenital disorders and their consequences for the children affected, their families and communities, and national health care systems, we propose priority measures that should be taken urgently to address this issue.

Abstract

Because Bangladesh intended to introduce pneumococcal conjugate vaccine (PCV)-10 in 2015, we examined the baseline burden of invasive pneumococcal disease (IPD) to measure impact of PCV.During 2007-2013, we performed blood and cerebrospinal fluid cultures in children <5 years old with suspected IPD identified through active surveillance at 4 hospitals. Isolates were serotyped by quellung and tested for antibiotic susceptibility by disc diffusion and E-test. Serotyping of culture-negative cases, detected by Binax or polymerase chain reaction, was done by sequential multiplex polymerase chain reaction. Trends in IPD case numbers were analyzed by serotype and clinical syndrome.The study identified 752 IPD cases; 78% occurred in children <12 months old. Serotype information was available for 78% (442/568), including 197 of 323 culture-negative cases available for serotyping. We identified 50 serotypes; the most common serotypes were 2 (16%), 1 (10 %), 6B (7%), 14 (7%) and 5 (7%). PCV-10 and PCV-13 serotypes accounted for 46% (range 29%-57% by year) and 50% (range 37%-64% by year) of cases, respectively. Potential serotype coverage for meningitis and nonmeningitis cases was 45% and 49% for PCV-10, and 48% and 57% for PCV-13, respectively. Eighty-two percent of strains were susceptible to all antibiotics except cotrimoxazole.The distribution of serotypes causing IPD in Bangladeshi children is diverse, limiting the proportion of IPD cases PCV can prevent. However, PCV introduction is expected to have major benefits as the country has a high burden of IPD-related mortality, morbidity and disability.

Abstract

Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed. In this paper we describe a shortened version of the VAI developed for the Population Health Metrics Research Consortium (PHMRC) Gold Standard Verbal Autopsy Validation Study using a systematic approach.We used data from the PHMRC validation study. Using the Tariff 2.0 method, we first established a rank order of individual questions in the PHMRC VAI according to their importance in predicting causes of death. Second, we reduced the size of the instrument by dropping questions in reverse order of their importance. We assessed the predictive performance of the instrument as questions were removed at the individual level by calculating chance-corrected concordance and at the population level with cause-specific mortality fraction (CSMF) accuracy. Finally, the optimum size of the shortened instrument was determined using a first derivative analysis of the decline in performance as the size of the VA instrument decreased for adults, children, and neonates.The full PHMRC VAI had 183, 127, and 149 questions for adult, child, and neonatal deaths, respectively. The shortened instrument developed had 109, 69, and 67 questions, respectively, representing a decrease in the total number of questions of 40-55%. The shortened instrument, with text, showed non-significant declines in CSMF accuracy from the full instrument with text of 0.4%, 0.0%, and 0.6% for the adult, child, and neonatal modules, respectively.We developed a shortened VAI using a systematic approach, and assessed its performance when administered using hand-held electronic tablets and analyzed using Tariff 2.0. The length of a VA questionnaire was shortened by almost 50% without a significant drop in performance. The shortened VAI developed reduces the burden of time and resources required for data collection and analysis of cause of death data in civil registration systems.

Abstract

Reliable data on the distribution of causes of death (COD) in a population are fundamental to good public health practice. In the absence of comprehensive medical certification of deaths, the only feasible way to collect essential mortality data is verbal autopsy (VA). The Tariff Method was developed by the Population Health Metrics Research Consortium (PHMRC) to ascertain COD from VA information. Given its potential for improving information about COD, there is interest in refining the method. We describe the further development of the Tariff Method.This study uses data from the PHMRC and the National Health and Medical Research Council (NHMRC) of Australia studies. Gold standard clinical diagnostic criteria for hospital deaths were specified for a target cause list. VAs were collected from families using the PHMRC verbal autopsy instrument including health care experience (HCE). The original Tariff Method (Tariff 1.0) was trained using the validated PHMRC database for which VAs had been collected for deaths with hospital records fulfilling the gold standard criteria (validated VAs). In this study, the performance of Tariff 1.0 was tested using VAs from household surveys (community VAs) collected for the PHMRC and NHMRC studies. We then corrected the model to account for the previous observed biases of the model, and Tariff 2.0 was developed. The performance of Tariff 2.0 was measured at individual and population levels using the validated PHMRC database.For median chance-corrected concordance (CCC) and mean cause-specific mortality fraction (CSMF) accuracy, and for each of three modules with and without HCE, Tariff 2.0 performs significantly better than the Tariff 1.0, especially in children and neonates. Improvement in CSMF accuracy with HCE was 2.5%, 7.4%, and 14.9% for adults, children, and neonates, respectively, and for median CCC with HCE it was 6.0%, 13.5%, and 21.2%, respectively. Similar levels of improvement are seen in analyses without HCE.Tariff 2.0 addresses the main shortcomings of the application of the Tariff Method to analyze data from VAs in community settings. It provides an estimation of COD from VAs with better performance at the individual and population level than the previous version of this method, and it is publicly available for use.

Abstract

Preterm birth is now the leading cause of under-five child deaths worldwide with one million direct deaths plus approximately another million where preterm is a risk factor for neonatal deaths due to other causes. There is strong evidence that kangaroo mother care (KMC) reduces mortality among babies with birth weight <2000 g (mostly preterm). KMC involves continuous skin-to-skin contact, breastfeeding support, and promotion of early hospital discharge with follow-up. The World Health Organization has endorsed KMC for stabilised newborns in health facilities in both high-income and low-resource settings. The objectives of this paper are to: (1) use a 12-country analysis to explore health system bottlenecks affecting the scale-up of KMC; (2) propose solutions to the most significant bottlenecks; and (3) outline priority actions for scale-up.The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops involved technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks", factors that hinder the scale-up, of maternal-newborn intervention packages. We used quantitative and qualitative methods to analyse the bottleneck data, combined with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for KMC.Marked differences were found in the perceived severity of health system bottlenecks between Asian and African countries, with the former reporting more significant or very major bottlenecks for KMC with respect to all the health system building blocks. Community ownership and health financing bottlenecks were significant or very major bottlenecks for KMC in both low and high mortality contexts, particularly in South Asia. Significant bottlenecks were also reported for leadership and governance and health workforce building blocks.There are at least a dozen countries worldwide with national KMC programmes, and we identify three pathways to scale: (1) champion-led; (2) project-initiated; and (3) health systems designed. The combination of all three pathways may lead to more rapid scale-up. KMC has the potential to save lives, and change the face of facility-based newborn care, whilst empowering women to care for their preterm newborns.

Abstract

Around one-third of the world's 2.8 million neonatal deaths are caused by infections. Most of these deaths are preventable, but occur due to delays in care-seeking, and access to effective antibiotic treatment with supportive care. Understanding variation in health system bottlenecks to scale-up of case management of neonatal infections and identifying solutions is essential to reduce mortality, and also morbidity.A standardised bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the development of the Every Newborn Action Plan. Country workshops involved technical experts to complete a survey tool, to grade health system "bottlenecks" hindering scale up of maternal-newborn intervention packages. Quantitative and qualitative methods were used to analyse the data, combined with literature review, to present priority bottlenecks and synthesise actions to improve case management of newborn infections.For neonatal infections, the health system building blocks most frequently graded as major or significant bottlenecks, irrespective of mortality context and geographical region, were health workforce (11 out of 12 countries), and community ownership and partnership (11 out of 12 countries). Lack of data to inform decision making, and limited funding to increase access to quality neonatal care were also major challenges.Rapid recognition of possible serious bacterial infection and access to care is essential. Inpatient hospital care remains the first line of treatment for neonatal infections. In situations where referral is not possible, the use of simplified antibiotic regimens for outpatient management for non-critically ill young infants has recently been reported in large clinical trials; WHO is developing a guideline to treat this group of young infants. Improving quality of care through more investment in the health workforce at all levels of care is critical, in addition to ensuring development and dissemination of national guidelines. Improved information systems are needed to track coverage and adequately manage drug supply logistics for improved health outcomes. It is important to increase community ownership and partnership, for example through involvement of community groups.

Taking on the gender challenge in organisations: what does it take?Global public healthHenry, S. K., Sandler, J., Passerini, L., Darmstadt, G. L.2015: 1-12

Abstract

Clear patterns emerged and are summarised on conditions for success in integrating a gender equality perspective across organisational programmes and culture. In short, organisations should consider five key 'ingredients' when designing their approach to integrating a gender equality perspective: (1) have a clear vision of success with measurable indicators; (2) have high-level, consistent, visible support; (3) take an intentional approach deeply rooted in the organisational culture and competencies; (4) ensure accountability at all levels and (5) invest both financial and technical resources. A vibrant community exists in virtually every region of the world of highly experienced gender equality experts that can support organisations on this path. Late adopters of integrating a gender equality perspective can benefit from decades of practice and a robust evidence base which has shifted focus among development organisations from asking 'why' addressing gender inequalities is important to learning 'how' to most effectively do this in programmes, policies, research and organisational culture while building a strong results framework.

Abstract

Neonatal mortality is increasingly concentrated globally in situations of conflict and political instability. In 1991, countries with high levels of political instability accounted for approximately 10% of all neonatal deaths worldwide; in 2013, this figure had grown to 31%. This has generated a "grand divergence" between those countries showing progress in neonatal mortality reduction compared to those lagging behind. We present new analyses demonstrating associations of neonatal mortality with political instability (r = 0.55) and poor governance (r = 0.70). However, heterogeneity in these relationships suggests that progress is possible in addressing neonatal mortality even in the midst of political instability and poor governance. In order to address neonatal mortality more effectively in such situations, we must better understand how specific elements of "strategic governance"-the minimal conditions of political stability and governance required for health service implementation-can be leveraged for successful introduction of specific health services. Thus, a more strategic approach to policy and program implementation in situations of conflict and political instability could lead to major accelerations in neonatal mortality reduction globally. However, this will require new cross-disciplinary collaborations among public health professionals, political scientists, and country actors.

Abstract

Progress in reducing newborn mortality has lagged behind progress in reducing maternal and child deaths. The Every Newborn Action Plan (ENAP) was launched in 2014, with the aim of achieving equitable and high-quality coverage of care for all women and newborns through links with other global and national plans and measurement and accountability frameworks. This article aims to assess country progress and the mechanisms in place to support country implementation of the ENAP. A country tracking tool was developed and piloted in October-December 2014 to collect data on the ENAP-related national milestones and implementation barriers in 18 high-burden countries. Simultaneously, a mapping exercise involving 47 semi-structured interviews with partner organizations was carried out to frame the categories of technical support available in countries to support care at and around the time of birth by health system building blocks. Existing literature and reports were assessed to further supplement analysis of country progress. A total of 15 out of 18 high-burden countries have taken concrete actions to advance newborn health; four have developed specific action plans with an additional six in process and a further three strengthening newborn components within existing plans. Eight high-burden countries have a newborn mortality target, but only three have a stillbirth target. The ENAP implementation in countries is well-supported by UN agencies, particularly UNICEF and WHO, as well as multilateral and bilateral agencies, especially in health workforce training. New financial commitments from development partners and the private sector are substantial but tracking of national funding remains a challenge. For interventions with strong evidence, low levels of coverage persists and health information systems require investment and support to improve quality and quantity of data to guide and track progress. Some of the highest burden countries have established newborn health action plans and are scaling up evidence based interventions. Further progress will only be made with attention to context-specific implementation challenges, especially in areas that have been neglected to date such as quality improvement, sustained investment in training and monitoring health worker skills, support to budgeting and health financing, and strengthening of health information systems.

Abstract

Despite significant advancements in the scientific evidence base of interventions to improve newborn survival, we have not yet been able to "bend the curve" to markedly accelerate global rates of reduction in newborn mortality. The ever-widening gap between discovery of scientific best practices and their mass adoption by families (the evidence-practice gap) is not just a matter of improving the coverage of health worker-community interactions. The design of the interactions themselves must be guided by sound behavioral science approaches such that they lead to mass adoption and impact at a large scale. The main barrier to the application of scientific approaches to behavior change is our inability to "unbox" the "black box" of family health behaviors in community settings. The authors argue that these are not black boxes, but in fact thoughtfully designed community systems that have been designed and upheld, and have evolved over many years keeping in mind a certain worldview and a common social purpose. An empathetic understanding of these community systems allows us to deconstruct the causal pathways of existing behaviors, and re-engineer them to achieve desired outcomes. One of the key reasons for the failure of interactions to translate into behavior change is our failure to recognize that the content, context, and process of interactions need to be designed keeping in mind an organized community system with a very different worldview and beliefs. In order to improve the adoption of scientific best practices by communities, we need to adapt them to their culture by leveraging existing beliefs, practices, people, context, and skills. The authors present a systems approach for community-centric design of interactions, highlighting key principles for achieving intrinsically motivated, sustained change in social norms and family health behaviors, elucidated with progressive theories from systems thinking, management sciences, cross-cultural psychology, learning and social cognition, and the behavioral sciences. These are illustrated through a case study of designing effective interactions in Shivgarh, India, that led to rapid and substantial changes in newborn health behaviors and reduction in NMR by half over a span of 16 months.

Abstract

Despite progress over the past decade in reducing the global burden of newborn deaths, gaps in the knowledge base persist, and means of translating empirical findings into effective policies and programs that deliver life-saving interventions remain poorly understood. Articles in this issue highlight the relevance of transdisciplinary research in perinatology and calls for increased efforts to translate research into public policy and to integrate interventions into existing primary care delivery systems. Given the complexity and multi-causality of many of the remaining challenges in newborn health, and the effects that social and economic factors have over many newborn conditions, it has further been proposed that integrated, multi-sector public policies are also required. In this article, we discuss the application of systems science methods to advance transdisciplinary research and public policy-making in perinatology. Such approaches to research and public policy have been used to address various global challenges but have rarely been implemented in developing country settings. We propose that they hold great promise to improve not only our understanding of complex perinatology problems but can also help translate research-based insights into effective, multi-pronged solutions that deliver positive, intended effects. Examples of successful transdisciplinary science exist, but successes and failures are context specific, and there are no universal blueprints or formulae to reproduce what works in a specific context into different social system settings. Group model building is a tool, based in the field of System Dynamics, that we have used to facilitate transdisciplinary research and, to a lesser extent, policy formulation in a systematic and replicable way. In this article, we describe how group model building can be used and argue for scaling its use to further the translation of empirical evidence and insights into policy and action that increase maternal and neonatal survival and well-being.

Abstract

High rates of child mortality and lost developmental potential in children under 5 years of age remain important challenges and drivers of inequity in the developing world. Substantive progress has been made toward Millennium Development Goal (MDG) 4 to improve child survival, but as we move into the post-2015 sustainable development agenda, much more work is needed to ensure that all children can realize their full and holistic physical, cognitive, psychological, and socio-emotional development potential. This article presents child survival and development as a continuous and multifaceted process and suggests that a life-course perspective of child development should be at the core of future policy making, programing, and research. We suggest that increased attention to child development, beyond child survival, is key to operationalize the sustainable development goals (SDGs), address inequities, build on the demographic dividend, and maximize gains in human potential. An important step toward implementation will be to increase integration of existing interventions for child survival and child development. Integrated interventions have numerous potential benefits, including optimization of resource use, potential additive impacts across multiple domains of health and development, and opportunity to realize a more holistic approach to client-centered care. However, a notable challenge to integration is the continued division between the health sector and other sectors that support child development. Despite these barriers, empirical evidence is available to suggest that successful multi-sectoral coordination is feasible and leads to improved short- and long-term outcomes in human, social, and economic development.

Abstract

Several studies show that maternal and neonatal/infant mortality risks increase with younger and older maternal age (<18 and >34 years), high parity (birth order >3), and short birth intervals (<24 months). Family planning programs are widely viewed as having contributed to substantial maternal and neonatal mortality decline through contraceptive use-both by reducing unwanted births and by reducing the burden of these high-risk births. However, beyond averting births, the empirical evidence for the role of family planning in reducing high-risk births at population level is limited. We examined data from 205 Demographic and Health Surveys (DHS), conducted between 1985 and 2013, to describe the trends in high-risk births and their association with the pace of progress in modern contraceptive prevalence rate (yearly increase in rate of MCPR) in 57 developing countries. Using Blinder-Oaxaca decomposition technique, we then examine the contributions of family planning program, economic development (GDP per capita), and educational improvement (secondary school completion rate) on the progress of MCPR in order to link the net contribution of family planning program to the reduction of high-risk births mediated through contraceptive use. Countries that had the fastest progress in improving MCPR experienced the greatest declines in high-risk births due to short birth intervals (<24 months), high parity births (birth order >3), and older maternal age (>35 years). Births among younger women <18 years, however, did not decline significantly during this period. The decomposition analysis suggests that 63% of the increase in MCPR was due to family planning program efforts, 21% due to economic development, and 17% due to social advancement through women's education. Improvement in MCPR, predominately due to family planning programs, is a major driver of the decline in the burden of high-risk births due to high parity, shorter birth intervals, and older maternal age in developing countries. The lack of progress in the decline of births in younger women <18 years of age underscores the need for more attention to ensure that quality contraceptive methods are available to adolescent women in order to delay first births. This study substantiates the significance of family planning programming as a major health intervention for preventing high-risk births and associated maternal and child mortality, but it highlights the need for concerted efforts to strengthen service provision for adolescents.

Abstract

The etiology of >90% of cases of suspected neonatal infection remains unknown. We conducted community-based surveillance in conjunction with hospital-based surveillance in a rural region in Bangladesh from June 2006 to September 2007 to assess the incidence and etiology of community-acquired viral infections among neonates.Community health workers (CHWs) assessed neonates at home on days 0, 2, 5 and 8 after birth and referred cases of suspected illness to the hospital (CHW surveillance). Among neonates with clinically suspected upper respiratory tract infection (URTI), pneumonia, sepsis and/or meningitis, virus identification studies were conducted on nasal wash, cerebrospinal fluid and/or blood specimens. In the hospital-based surveillance, similar screening was conducted among all neonates (referred by CHWs and self-referred) who were admitted to the hospital.CHW surveillance found an incidence rate of 15.6 neonatal viral infections per 1000 live births with 30% of infections identified on the day of birth. Among neonates with suspected sepsis, a viral etiology was identified in 36% of cases, with enterovirus accounting for two-thirds of those infections. Respiratory syncytial virus was the most common etiologic agent among those with viral pneumonia (91%) and URTI (68%). There was a low incidence (1.2%) of influenza in this rural population.Viral infections are commonly associated with acute newborn illness, even in the early neonatal period. The estimated incidence was 5-fold greater than reported previously for bacterial infections. Low-cost preventive measures for neonatal viral infections are urgently needed.

Abstract

South Asian studies, including those from Nepal, have documented increased risk of neonatal mortality among girls, despite their early biologic survival advantage. We examined sex differences in neonatal morbidity and care-seeking behavior to determine whether such differences could help explain previously observed excess late neonatal mortality among girls in Nepal.A secondary analysis of data from a trial of chlorhexidine use among neonates in rural Nepal was conducted. The objective was to examine sex differences in neonatal morbidity and care-seeking behavior for ill newborns. Girls were used as the reference group.Referral for care was higher during the early neonatal period (ENP: 0-7 days old) (50.7%) than the late neonatal period (LNP: 8-28 days old) (31.3%), but was comparable by sex. There were some significant differences in reasons for referral by sex. Boys were significantly more often referred for convulsions/stiffness, having yellow body/eyes, severe skin infection, and having at least two of the following: difficulty breathing, difficulty feeding, fever, or vomiting during the ENP. Girls were more often referred for hypothermia. During the LNP, boys were significantly more often referred for having yellow body/eyes, persistent watery stool, and severe skin infection. There were no referral types in the LNP for which girls were more often referred. Less than half of those referred at any point were taken for care (47.0%) and referred boys were more often taken than girls (Neonatal Period OR: 1.77, 95% CI: 1.64 - 1.91). Family composition differentially impacted the relationship between care-seeking and sex. The greatest differences were in families with only prior living girls (Pahadi - ENP OR: 1.78, 95% CI: 1.29 - 2.45 and LNP OR: 1.51, 95% CI: 1.03 - 2.21; Madeshi - ENP OR: 2.86, 95% CI: 2.28 - 3.59 and LNP OR: 2.45, 95% CI: 1.84 - 3.26).Care-seeking was inadequate for both sexes, but ill boys were consistently more often taken for care than girls, despite comparable referral. Behavioral interventions to improve care-seeking, especially in the early neonatal period, are needed to improve neonatal survival. Addressing gender bias in care-seeking, explicitly and within interventions, is essential to reducing neonatal mortality differentials between boys and girls.

Abstract

Validate a tool to determine neurodevelopmental impairments (NDIs) in >2- to 5-year-old children in a country with limited child development expertise.Rapid Neurodevelopmental Assessment (RNDA) is a tool designed to detect functional status and NDIs across multiple neurodevelopmental domains. Validity was determined in 77 children enrolled by door-to-door sampling in Dhaka and who were administered the RNDA by 1 of 6 testers (4 developmental therapists, 2 special education teachers) and simultaneously administered a test of adaptive behavior (AB; Independent Behavior Assessment Scale) and intelligence quotient (IQ) tests (Bayley Scales of Infant Development II, Stanford Binet Intelligence Scale, Wechsler Preschool and Primary Scales of Intelligence) by psychologists.Interrater reliability ranged from good to excellent. There were significant differences in AB in mean percentile scores on the Independent Behavior Assessment Scale for motor (P = .0001), socialization (P = .001), communication (P = .001), and full-scale (P = .001) scores in children with ?1 NDI ("any NDI") versus no NDI. Significant differences in those with versus those without "any NDI" were found on IQ scores. Sensitivity and specificity for "significant difficulties" (defined as AB z-scores < -2 SDs and/or IQ <70) and "mild difficulties included" (AB z-scores < -1SD and/or IQ <85) were 90% and 60% and 80% and 76%, respectively.The RNDA validity results are promising for use by child care professionals in field and clinical settings, but the tool needs further replication and refinement for assessment of specific impairments of vision, hearing, and seizures.

Abstract

Verbal autopsy (VA) is used to ascertain cause-specific neonatal mortality using parental/familial recall. We sought to compare agreement between causes of death obtained from the VA by physician review vs. computer-based algorithms. Data were drawn from a cluster-randomised trial involving 4130 live-born infants and 167 neonatal deaths in the rural Sarlahi District of Nepal. We examined the agreement between causes ascertained by physician review and algorithm assignment by the kappa (kappa) statistic. We also compared responses to identical questions posed posthumously during neonatal VA interviews with those obtained during maternal interviews and clinical examinations regarding condition of newborns soon after birth. Physician reviewers assigned prematurity or acute lower respiratory infection (ALRI) as causes of 48% of neonatal deaths; 41% were assigned as uncertain. The algorithm approach assigned sepsis (52%), ALRI (31%), birth asphyxia (29%), and prematurity (24%) as the most common causes of neonatal death. Physician review and algorithm assignment of causes of death showed high kappa for prematurity (0.73), diarrhoea (0.81) and ALRI (0.68), but was low for congenital malformation (0.44), birth asphyxia (0.17) and sepsis (0.00). Sensitivity and specificity of VA interview questions varied by symptom, with positive predictive values ranging from 50% to 100%, when compared with maternal interviews and examinations of neonates soon after birth. Analysis of the VA data by physician review and computer-based algorithms yielded disparate results for some causes but not for others. We recommend an analysis technique that combines both methods, and further validation studies to improve performance of the VA for assigning causes of neonatal death.

Abstract

This article reviews in detail the pathogenesis, clinical characteristics and management of impetigo in children. Impetigo is the most common bacterial skin infection of children. Most cases of nonbullous impetigo and all cases of bullous impetigo are caused by Staphylococcus aureus. The remainder of cases of nonbullous impetigo are due to group A beta hemolytic streptococci (GABHS). GABHS colonize the skin directly by binding to sites on fibronectin that are exposed by trauma. In contrast, S. aureus colonizes the nasal epithelium first; from this reservoir, colonization of the skin occurs. Patients with recurrent impetigo should be evaluated for carriage of S. aureus. Superficial, localized impetigo may be treated successfully in more than 90% of cases with topical application of mupirocin ointment. Impetigo that is widespread or involves deeper tissues should be treated with a beta-lactamase-resistant oral antibiotic. The choice of antibiotics is affected by the local prevalence of resistance to erythromycin among strains of S. aureus, antibiotic cost and availability, and issues of compliance.